The Environmental Determinants of Diabetes in the Young (TEDDY), a multicenter prospective cohort study, was initiated in 2003 to identify environmental factors that trigger or protect against the development of islet autoimmunity and type 1 diabetes (T1D). A successful study outcome should allow better understanding of the etiology and pathogenesis of T1D and the development of new strategies to prevent, delay, or reverse the disease. Newborns are screened by HLA-DR,DQ genotyping to identify those at increased risk for T1D. Eligible children are followed four times per year until 4 years of age and twice a year thereafter until 15 years of age. The specific aims of the GA/FL Clinical Center renewal application are to: 1) Complete our contribution to the HLA-DR,DQ screening of 361,000 newborns and enrollment of 7,800 high-risk infants into intensive prospective follow-up to achieve the overall TEDDY goals, 2) Refine strategies to retain subjects enrolled in the follow-up and collect all planned biological specimens and epidemiological data according to the standard protocol including close monitoring of performance and sample/data quality, 3) Ascertain prospectively development of islet autoantibodies and clinical T1D in the study subjects, 4) Perform planned laboratory tests at appropriate times using a nested case-control study design to answer specific scientific questions and hypotheses pertinent to the TEDDY study goals, 5) Analyze and publish laboratory and epidemiological data in collaboration with other TEDDY clinical centers and the Data Coordinating Center, 6) Guide the ongoing TEDDY project by participation of the Clinical Center investigators and staff in work of the study Steering Committee and sub-committees. These proposed activities are essential to achieve the following long-term scientific goals: 1) To identify environmental factors (infectious, dietary, psychosocial factors, toxins, allergens, etc) that trigger or protect against the development of islet autoantibodies or T1 D. 2) To assess potential gene-environment interactions to improve identification of environmental factors affecting development of islet autoimmunity or T1D, and to gain insight on mechanisms. 3) Collect and bank specimens for studies of T1D pathogenesis and development of biomarkers for T1D prediction. The prospectively collected specimens on TEDDY subjects provide a unique opportunity for scientists within and outside the TEDDY consortium to test novel hypotheses by performing otherwise impossible critical studies. [unreadable] [unreadable]